Search

Abstract We apply machine learning models to a universe of 20,185 finance articles published between 1976 and 2015 on 17 finance journals, and objectively identify 38 research topics. The financial crisis, hedge/mutual fund, social network, and culture were the fastest growing topics, while market microstructure, initial public offering, and option pricing shrank most from 2006 to 2015. We also list each topic's most cited papers, and present the fastest‐growing topics among the universe of 130,547 SSRN working papers. Moreover, we find a bibliometric regularity: the number of researchers covering n topics is about twice the number of researchers covering n + 1 topics.

Background: A predominate azole-resistant Candida tropicalis clade 4 genotype causing candidemia has been detected in not only Taiwan but also China, Singapore, and Australia. It can also be detected on fruit surfaces. In addition to determining distribution and drug susceptibilities of pathogenic yeasts in environments of intensive care units of 25 hospitals in Taiwan, we would also like to investigate whether the azole-resistant C. tropicalis exists in Taiwan's hospital environment. Methods: The swabs of hospital environments were collected from August to November in 2020 and were cultured for yeasts. The yeasts were identified by rDNA sequence and the antifungal susceptibilities of those isolates were determined by the broth microdilution method. Results: The average yeast-culture rate of hospitals was 9.4% (217/2299). Sinks had the highest yeast-positive culture rate (32.7%), followed by bedside tables (28.9%), floors (26.0%), water-dispenser buttons (23.8%), and TV controller/touch panels (19.0%). Of 262 identified isolates, Candida parapsilosis was the most common species, accounting for 22.1%, followed by Filobasidium uniguttulatum (18.3%), Candida albicans (9.5%), C. tropicalis (8.0%), Candida glabrata (Nakaseomyces glabratus) (6.9%), and 30 other species (35.1%). Of the 21 C. tropicalis isolates from 11 units in 9 hospitals, 15 diploid sequence types (DSTs) were identified. The two DST506 fluconazole-resistant ones belonged to clade 4. Conclusion: We detected not only various pathogenic yeast species but also the predominant clade 4 genotype of azole-resistant C. tropicalis. Our findings highlight and re-emphasize the importance of regular cleaning and disinfection practices.

Abstract Background Blood cultures are essential for diagnosing bloodstream infections, but current phenotypic tests for antimicrobial resistance (AMR) provide limited information. Oxford Nanopore Technologies introduces nanopore sequencing with adaptive sampling, capable of real-time host genome depletion, yet its application directly from blood cultures remains unexplored. This study aimed to identify pathogens and predict AMR using nanopore sequencing. Methods In this cross-sectional genomic study, 458 positive blood cultures from bloodstream infection patients in central Taiwan were analyzed. Parallel experiments involved routine microbiologic tests and nanopore sequencing with a 15-h run. A bioinformatic pipeline was proposed to analyze the real-time sequencing reads. Subsequently, a comparative analysis was performed to evaluate the performance of species identification and AMR prediction. Results The pipeline identified 76 species, with 88 Escherichia coli, 74 Klebsiella pneumoniae, 43 Staphylococcus aureus, and 9 Candida samples. Novel species were also discovered. Notably, precise species identification was achieved not only for monomicrobial infections but also for polymicrobial infections, which was detected in 23 samples and further confirmed by full-length 16S rRNA amplicon sequencing. Using a modified ResFinder database, AMR predictions showed a categorical agreement rate exceeding 90% (3799/4195) for monomicrobial infections, with minimal very major errors observed for K. pneumoniae (2/186, 1.1%) and S. aureus (1/90, 1.1%). Conclusions Nanopore sequencing with adaptive sampling can directly analyze positive blood cultures, facilitating pathogen detection, AMR prediction, and outbreak investigation. Integrating nanopore sequencing into clinical practices signifies a revolutionary advancement in managing bloodstream infections, offering an effective antimicrobial stewardship strategy, and improving patient outcomes.

Abstract This study elucidates the in vivo genetic mechanisms contributing to the emerging resistance to carbapenem in Shewanella algae through a lens of adaptive microbial evolution. Leveraging PacBio amplification-free sequencing, we tracked the evolution of β-lactam resistance in clinical isolates from a persistent S. algae bacteremia case amidst antimicrobial therapy. Our investigation spotlighted a recurrent G547W mutation in the sensor histidine kinase (pdsS), which was associated with the overexpression of an OmpA-like protein (pdsO) within a proteobacteria-specific sortase system. Intriguingly, we observed a recurrent switch between wild-type and G547W alleles, revealing an adaptive expansion and contraction of underlying cell subpopulations in response to β-lactam exposure. Comparative transcriptome analyses further demonstrated the overexpression of genes pivotal for membrane integrity, biofilm formation, immune evasion, and β-lactamase activation in resistant samples. This underscores the pre-existence of resistant cells at minuscule frequencies even without antibiotic pressure, potentially explaining the within-host emergence of resistance during antibiotic treatments. Our findings provide pivotal insights into the dynamic genetic adaptations of S. algae under therapeutic pressures, unmasking intricate resistance mechanisms and highlighting the critical role of subpopulation dynamics in treatment outcomes.

ABSTRACTDietary patterns and corresponding gut microbiota profiles are associated with various health conditions. A diet rich in polyphenols, primarily plant-based, has been shown to promote the growth of probiotic bacteria in the gastrointestinal tract, subsequently reducing the risk of metabolic disorders in the host. The beneficial effects of these bacteria are largely due to the specific metabolites they produce, such as short-chain fatty acids and membrane proteins. In this study, we employed a metabolomics-guided bioactive metabolite identification platform that included bioactivity testing using in vitro and in vivo assays to discover a bioactive metabolite produced from probiotic bacteria. Through this approach, we identified 5’-methylthioadenosine (MTA) as a probiotic bacterial-derived metabolite with anti-obesity properties. Furthermore, our findings indicate that MTA administration has several regulatory impacts on liver functions, including modulating fatty acid synthesis and glucose metabolism. The present study elucidates the intricate interplay between dietary habits, gut microbiota, and their resultant metabolites.

ABSTRACT Coccidiosis, caused by Eimeria parasites, significantly impacts poultry farm economics and animal welfare. Beyond its direct impact on health, Eimeria infection disrupts enteric microbial populations leading to dysbiosis and increases vulnerability to secondary diseases such as necrotic enteritis, caused by Clostridium perfringens. The impact of Eimeria infection or anticoccidial vaccination on host gastrointestinal phenotypes and enteric microbiota remains understudied. In this study, the metabolomic profiles and microbiota composition of chicken caecal tissue and contents were evaluated concurrently during a controlled experimental vaccination and challenge trial. Cobb500 broilers were vaccinated with a Saccharomyces cerevisiae-vectored anticoccidial vaccine and challenged with 15,000 Eimeria tenella oocysts. Assessment of caecal pathology and quantification of parasite load revealed correlations with alterations to caecal microbiota and caecal metabolome linked to infection and vaccination status. Infection heightened microbiota richness with increases in potentially pathogenic species, while vaccination elevated beneficial Bifidobacterium. Using a multi-omics factor analysis, data on caecal microbiota and metabolome were integrated and distinct profiles for healthy, infected, and recovering chickens were identified. Healthy and recovering chickens exhibited higher vitamin B metabolism linked to short-chain fatty acid-producing bacteria, whereas essential amino acid and cell membrane lipid metabolisms were prominent in infected and vaccinated chickens. Notably, vaccinated chickens showed distinct metabolites related to the enrichment of sphingolipids, important components of nerve cells and cell membranes. Our integrated multi-omics model revealed latent biomarkers indicative of vaccination and infection status, offering potential tools for diagnosing infection, monitoring vaccination efficacy, and guiding the development of novel treatments or controls.IMPORTANCEAdvances in anticoccidial vaccines have garnered significant attention in poultry health management. However, the intricacies of vaccine-induced alterations in the chicken gut microbiome and its subsequent impact on host metabolism remain inadequately explored. This study delves into the metabolic and microbiotic shifts in chickens post-vaccination, employing a multi-omics integration analysis. Our findings highlight a notable synergy between the microbiome composition and host-microbe interacted metabolic pathways in vaccinated chickens, differentiating them from infected or non-vaccinated cohorts. These insights pave the way for more targeted and efficient approaches in poultry disease control, enhancing both the efficacy of vaccines and the overall health of poultry populations.

Abstract Dietary emulsifiers are linked to various diseases. The recent discovery of the role of gut microbiota–host interactions on health and disease warrants the safety reassessment of dietary emulsifiers through the lens of gut microbiota. Lecithin, sucrose fatty acid esters, carboxymethylcellulose (CMC), and mono- and diglycerides (MDG) emulsifiers are common dietary emulsifiers with high exposure levels in the population. This study demonstrates that sucrose fatty acid esters and carboxymethylcellulose induce hyperglycemia and hyperinsulinemia in a mouse model. Lecithin, sucrose fatty acid esters, and CMC disrupt glucose homeostasis in the in vitro insulin-resistance model. MDG impairs circulating lipid and glucose metabolism. All emulsifiers change the intestinal microbiota diversity and induce gut microbiota dysbiosis. Lecithin, sucrose fatty acid esters, and CMC do not impact mucus–bacterial interactions, whereas MDG tends to cause bacterial encroachment into the inner mucus layer and enhance inflammation potential by raising circulating lipopolysaccharide. Our findings demonstrate the safety concerns associated with using dietary emulsifiers, suggesting that they could lead to metabolic syndromes.

Abstract Introduction Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. This clinical study aimed to evaluate its antiviral efficacy of ropeginterferon alfa-2b against SARS-CoV-2 infection. Methods This is a multicenter, randomized, open-label study. Adult patients with confirmed SARS-CoV-2 infection with initial cycle threshold (Ct) value

Ceftazidime-avibactam (CAZ-AVI) has been launched in Asian countries for five years, local real-world data about infections, patient characteristics, efficacy, and safety of CAZ-AVI in gram-negative bacterial infection is limited. We conducted a multicenter, retrospective cohort study to investigate the clinical characteristics, microbiology, and outcomes of patients treated with CAZ-AVI for gram-negative bacterial infection in Taiwan. Among the 472 patients treated by CAZ-AVI, 44.9% had respiratory tract infections, 21.2% had complicated urinary tract infections, 12.5% had complicated intra-abdominal infections, and 9.5% had primary bacteremia. Most patients receiving ceftazidime/avibactam in Taiwan are older, have a high SOFA score (mean 8.4), and have a high Charlson Comorbidity Index score (75.1%). 90% (425/472) of CAZ-AVI were used as targeted therapy for pathogens including Klebsiella pneumoniae (304/472, 64.4%), Pseudomonas aeruginosa (84/472, 17.8%), Escherichia coli (39/472, 8.3%), and Enterobacter spp. (11/472, 2.3%). The overall clinical success rate is 58.1%, and the in-hospital mortality rate is 41.1%. The logistic regression model revealed a significantly higher clinical success rate for those who initiated CAZ-AVI within 24 - 48 hours than those receiving CAZ-AVI > 72 hours. The multivariate logistic regression analysis revealed that receiving immunomodulators, higher SOFA score, and Enterobacter spp. infection were the significant factors associated with in-hospital mortality.

AIM: We aim to investigate the antimicrobial susceptibility, and the clinical and genetic characteristics of urinary tract infections (UTIs) caused by Achromobacter species. BACKGROUND: UTIs due to Achromobacter species are uncommon. Until now, there has been limited data available. METHODS: We retrospectively analyzed forty-seven Achromobacter isolates from eighteen patients in a tertiary hospital in Taiwan from 2022 to 2023. RESULTS: Fifteen patients (83%) were male, and the median [IQR] age was 69 [64-80] years. Solid or hematological malignancies were the most frequent underlying diseases (seven cases, 39%). Fourteen patients (78%) had urological abnormalities. Almost all isolates were susceptible to piperacillin-tazobactam (98%) and ceftazidime (96%). 85% were susceptible to imipenem, and 72% were susceptible to trimethoprim-sulfamethoxazole. Low frequencies of susceptibility to cefepime (10%), ciprofloxacin (6%), amikacin (4%), gentamicin (2%), and ceftriaxone (0) were observed. blaOXA-114, a constitutive chromosomal β-lactamase, was also detected in most of the Achromobacter isolates through whole genome sequencing. Four patients (22%) had co-infection with other bacteria in the urinary tract. Eleven patients (61%) received appropriate antibiotics at diagnosis. The general clinical outcome was favorable, and only one patient died within thirty days of diagnosis due to receiving palliative care for terminal malignancy. However, recurrence occurred in eight patients (44%) with urological abnormalities. CONCLUSIONS: UTIs caused by Achromobacter species were primarily seen in elderly individuals with underlying conditions, notably urological abnormalities and malignancies. Managing these infections can be challenging due to high antibiotic resistance and recurrence rates. Piperacillin-tazobactam may be prioritized for treatment.

Snakebite envenomings continue to represent a major public health concern in Taiwan because of the presence of various venomous snakes whose habitats intersect with human activities. This review provides a comprehensive analysis of the clinical characteristics, complications, and management strategies associated with snakebite envenomings in Taiwan. Taiwan is inhabited by six principal venomous snakes: Trimeresurus stejnegeri stejnegeri, Protobothrops mucrosquamatus, Deinagkistrodon acutus, Daboia siamensis, Naja atra, and Bungarus multicinctus, each presenting distinct clinical challenges. The clinical manifestations vary from local symptoms such as pain, swelling, and necrosis to systemic complications including neurotoxicity, coagulopathy, and organ failure, depending on the species. Notable complications arising from these snakebite envenomings include necrotizing soft tissue infection, compartment syndrome, respiratory failure, and acute kidney injury, often necessitating intensive medical interventions. This review highlights the critical importance of early diagnosis, the prompt administration of antivenoms, and multidisciplinary care to improve patient outcomes and reduce healthcare costs. Future research is encouraged to enhance treatment efficacy, improve public awareness, and develop targeted prevention strategies. By identifying gaps in current knowledge and practice, this work contributes to the global literature on envenoming management and serves as a foundation for advancing clinical protocols and reducing snakebite-related morbidity and mortality in Taiwan.

Metabolomics research provides a clearer understanding of an organism’s metabolic state and enables a more accurate representation of its functional performance. This study aimed to investigate changes in the metabolome of lung tissues resulting from prenatal exposure to polystyrene microplastics (PS-MPs) and to understand the underlying mechanisms of lung damage in rat offspring. We conducted metabolomic analyses of lung tissue from seven-day-old rat pups exposed to prenatal PS-MPs. Our findings revealed that prenatal exposure to PS-MPs led to significantly increased oxidative stress in lung tissues, characterized by notable imbalances in nucleic acid metabolism and altered profiles of specific amino acids. Furthermore, we evaluated the therapeutic effects of melatonin treatment on lung function in 120-day-old offspring and found that melatonin treatment significantly improved lung function and histologic change in the affected offspring. This study provides valuable biological insights into the mechanisms underlying lung damage caused by prenatal PS-MPs exposure. Future studies should focus on validating the results of animal experiments in humans, exploring additional therapeutic mechanisms of melatonin, and developing suitable protocols for clinical use.

Abstract Background Hyperactive neutrophil extracellular traps (NETs) formation plays a key role in the pathogenesis of severe COVID-19. Extracellular vesicles (EVs) are vehicles which carry cellular components for intercellular communication. The association between COVID-19 patients-derived EVs and NETs formation remains elusive. Methods We explored the roles of EVs in NETs formation from 40 COVID-19 patients with different disease severities as well as 30 healthy subjects. The EVs-carried microRNAs profile was analyzed using next generation sequencing approach which was validated by quantitative reverse transcription PCR. The regulatory mechanism of EVs on NETs formation was investigated by using an in vitro cell-based assay, including immunofluorescence assay, flow cytometry, and immunoblotting. Results COVID-19 patient–derived EVs induced NETs formation by endocytosis uptake. SARS-CoV-2 spike protein-triggered NETs formation was significantly enhanced in the presence of platelet–derived EVs (pEVs) and this effect was Toll-like receptor (TLR) 7/8- and NADPH oxidase-dependent. Increased levels of miR-21/let-7b were revealed in EVs from COVID-19 patients and were associated with disease severity. We demonstrated that the spike protein activated platelets directly, followed by the subsequent intracellular miR-21/let-7b upregulation and then were loaded into pEVs. The pEVs-carried miR-21 interacted with TLR7/8 to prime p47phox phosphorylation in neutrophils, resulting in NADPH oxidase activation to promote ROS production and NETs enhancement. In addition, miR-21 modulates NF-κB activation and IL-1β/TNFα/IL-8 upregulation in neutrophils upon TLR7/8 engagement. The miR-21 inhibitor and TLR8 antagonist could suppress efficiently spike protein-induced NETs formation and pEVs primed NETs enhancement. Conclusions We identified SARS-CoV-2 triggered platelets–derived GU-enriched miRNAs (e.g., miR-21/let-7b) as a TLR7/8 ligand that could activate neutrophils through EVs transmission. The miR-21-TLR8 axis could be used as a potential predisposing factor or therapeutic target for severe COVID-19.

Plants are associated with a large diversity of microbes, and these complex plant-associated microbial communities are critical for plant health. Welsh onion (Allium fistulosum L.) is one of the key and oldest vegetable crops cultivated in Taiwan. The leaf of the Welsh onion is one of the famous spices in Taiwanese cuisine, thus, it is crucial to control foliar diseases. In recent years, Welsh onion cultivation in Taiwan has been severely threatened by the occurrence of leaf blight disease, greatly affecting their yield and quality. However, the overall picture of microbiota associated with the Welsh onion plant is still not clear as most of the recent etiological investigations were heavily based on the isolation of microorganisms from diseased plants. Therefore, studying the diversity of fungal communities associated with the leaf blight symptoms of Welsh onion may provide information regarding key taxa possibly involved in the disease. Therefore, this investigation was mainly designed to understand the major fungal communities associated with leaf blight to identify key taxa potentially involved in the disease and further evaluate any shifts in both phyllosphere and rhizosphere mycobiome assembly due to foliar pathogen infection by amplicon sequencing targeting the Internal Transcribed Spacer (ITS) 1 region of the rRNA. The alpha and beta-diversity analyses were used to compare the fungal communities and significant fungal groups were recognized based on linear discriminant analyses. Based on the results of relative abundance data and co-occurrence networks in symptomatic plants we revealed that the leaf blight of Welsh onion in Sanxing, is a disease complex mainly involving Stemphylium and Colletotrichum taxa. In addition, genera such as Aspergillus, Athelia and Colletotrichum were abundantly found associated with the symptomatic rhizosphere. Alpha-diversity in some fields indicated a significant increase in species richness in the symptomatic phyllosphere compared to the asymptomatic phyllosphere. These results will broaden our knowledge of pathogens of Welsh onion associated with leaf blight symptoms and will assist in developing effective disease management strategies to control the progress of the disease.

Corals and their associated microbiota form a “holobiont,” which includes symbiotic algae and other associated microbiota dominated by bacteria. The composition of holobiont is influenced by various environmental factors, such as increasing sea water temperatures. Previous studies of the effects of temperature changes on coral physiology and associated bacterial communities have been conducted based on stable water temperatures set by mean temperatures, or by slowly increasing/decreasing temperatures. However, the daily temperature fluctuations that corals experience in nature are not stable. The current understanding of the effects of large daily temperature fluctuations on coral and associated bacterial community dynamics is limited. Hence, we conducted a four-week tank experiment using different large daily temperature fluctuations (±5 °C and ±7 °C) accompanied by continuous warming conditions (26 °C to 29 °C) to investigate the effects on two common reef-building corals, Stylophora pistillata and Pocillopora acuta. During the experiment, the activity of coral host catalase and superoxide dismutase were measured, the photosynthetic ability of symbiotic algae was recorded, and the variation in bacterial communities was analyzed using the V6-V8 region of 16S rDNA. According to the results, different parts of the holobionts of two coral species exhibited varying response rates to the continuous warming conditions and diurnal temperature fluctuations. Additionally, it was found that diurnal temperature fluctuations may mitigate the heat stress on the host and reduce the changes in bacterial response to warming. Therefore, it is suggested that the holobionts of different coral species may adopt different adaptation and survival strategies in response to diurnal temperature fluctuations and warming. Finally, based on the response of these two coral species under the conditions of diurnal temperature fluctuations and continuous warming, Acinetobacter and Rhodobacteraceae were identified as potential indicator coral-associated bacteria. This is the first study to investigate the tripartite dynamic response of coral, symbiotic algae and bacteria to daily temperature fluctuations.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

Abstract Background Venomous snakebites induce tissue destruction and secondary infection; however, the optimal timing of surgical intervention for these complications remains unknown. This study assessed the clinical predictors of early surgical intervention in patients with snakebites. Methods This retrospective study included 63 patients (45 men and 18 women) with venomous snakebites. In addition to the snake species, the demographics, affected body parts, clinical characteristics, and ultrasound findings of the patients in the surgical (32 patients) and nonsurgical (31 patients) groups were analyzed and compared. Results A higher incidence of acute compartment syndrome, local ecchymosis, skin necrosis, bullae, blisters, and fever was found in the surgical group than in the nonsurgical group, and ultrasound findings of the absence of Doppler flow were more frequently noted in the surgical group than in the nonsurgical group. After adjustment using a multivariate logistic regression model, only advanced age, Naja atra bite, local ecchymosis, and bulla or blister formation remained significant factors for surgical intervention. Furthermore, comparison of the outcomes of patients who received early (≤ 24 h) and late (> 24 h) surgical intervention revealed that the duration of continuous negative pressure wound therapy (6 vs. 15 days; P = 0.006), duration of hospital stay (13 vs. 26 days; P = 0.002), and duration of outpatient follow-up (15 vs. 36 days; P

ABSTRACT We report that carbapenem resistance developed in an extensively drug-resistant Salmonella enterica serovar Agona strain during antimicrobial therapy and in an AmpC β-lactamase-producing S. Infantis strain. Whole-genome sequence analysis indicated that carbapenem resistance in the S. Agona strain was associated with the insertion of a 160-kb IS15DI composite transposon in ompC_378, which encodes a porin consisting of 378 amino acids, along with a 397-bp deletion in the ompD. The transposon harbored 12 resistance genes including bla CTX-M-55 and an efflux pump regulatory gene, ramAp. Carbapenem resistance in the bla CMY-2-carrying S. Infantis strain was linked to the insertion of a 22,905-bp segment located 10 bp upstream of the ompC_378 coding sequence, as well as a 254-bp deletion in ompD. Our findings indicate that the loss of both ompC_378 and ompD is necessary for carbapenem resistance in extended-spectrum β-lactamase and AmpC β-lactamase-producing Salmonella strains. IMPORTANCE Carbapenem resistance arising from the loss of porins is commonly observed in extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase-producing strains of certain Enterobacteriaceae genera, including Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. However, this resistance mechanism is rarely reported in the Salmonella genus. To address this knowledge gap, our study offers genetic evidence demonstrating that the loss of two specific porins (OmpC_378 and OmpD) is crucial for the development of carbapenem resistance in Salmonella ESBL and AmpC β-lactamase-producing strains. Furthermore, our findings reveal that most Salmonella serovars carry seven porin parathologs, with OmpC_378 and OmpD being the key porins involved in the development of carbapenem resistance in Salmonella strains.

Identifying farming practices that decrease susceptibility to infectious diseases and optimise food conversion efficiency is valuable for chicken welfare and productivity, the environment, and public health. Enterotypes can be used to define microbial community phenotypes that have differential, potentially significant impacts on gut health. In this study, we delineated enterotypes by analysing the microbiomes of 300 indigenous Kadaknath and 300 commercial Cobb400 broiler chickens raised across 60 farms in western India. Using a compositional data approach, we identified three distinct enterotypes: PA1 (n=290), PA2 (n=142) and PA3 (n=67). PA1 and PA2 clustered more closely with each other than with PA3, however, PA2 had significantly lower alpha diversity than PA1. PA1 had a high Firmicutes: Bacteroides ratio, was dominated by Faecalibacterium and had a higher abundance of Prevotellamassilia than other enterotypes. PA2 was characterised by its low alpha diversity, a high abundance of the common taxa Phascolarctobacterium A and Phocaeicola dorei and a significantly higher Campylobacter abundance than PA1. PA3 had the highest Bacteroidota abundance of the three enterotypes and was defined by high prevalence of lower abundance taxa such as CAG-831 and Mucispirillum schaedleri. Network analysis showed that all enterotypes have different proportions of competing Firmicutes-dominant and Bacteroidota-dominant guilds. Random Forest Modelling using defined farm characteristics was predictive for enterotype. Factors affecting enterotype include whether farms were open, enclosed or caged, the location of farms, whether visitors were allowed inside, the number of people in contact with the chickens, chicken line, the presence of dogs and whether flock thinning took place. This study suggests that enterotypes are influenced by farming practices, hence modification of practices could potentially be used to reduce the burden of zoonotic pathogens such as Campylobacter.

Microbiota tryptophan metabolism and the biosynthesis of indole derivatives play an important role in homeostasis and pathogenesis in the human body and can be affected by the gut microbiota. However, studies on the interplay between gut microbiota and tryptophan metabolites in patients undergoing dialysis are lacking. This study aimed to identify the gut microbiota, the indole pathway in tryptophan metabolism, and significant functional differences in ESRD patients with regular hemodialysis. We performed the shotgun metagenome sequencing of stool samples from 85 hemodialysis patients. Using the linear discriminant analysis effect size (LEfSe), we examined the composition of the gut microbiota and metabolic features across varying concentrations of tryptophan and indole metabolites. Higher tryptophan levels promoted tyrosine degradation I and pectin degradation I metabolic modules; lower tryptophan levels were associated with glutamate degradation I, fructose degradation, and valine degradation modules. Higher 3-indoxyl sulfate concentrations were characterized by alanine degradation I, anaerobic fatty acid beta-oxidation, sulfate reduction, and acetyl-CoA to crotonyl-CoA. Contrarily, lower 3-indoxyl sulfate levels were related to propionate production III, arabinoxylan degradation, the Entner–Doudoroff pathway, and glutamate degradation II. The present study provides a better understanding of the interaction between tryptophan, indole metabolites, and the gut microbiota as well as their gut metabolic modules in ESRD patients with regular hemodialysis.

Objective: Shewanella algae is a zoonotic marine bacterium that causes a variety of infections in immunocompromised patients or those who have been exposed to seawater. The development of trimethoprim/sulfamethoxazole (TMP/SMX) resistance in S. algae are found in human and environment isolates during the past ten years, and thus the treatment options are decreasing. Methodology: In the study, we conduct a comparative genomic study to identify the resistant mechanism of TMP/SMX-resistance in S. algae. Results: We found the resistance of TMP/SMX in S. algae is associated with the existence of sul1 and dfrA12 within the class 1 integron. The gene cassette dfra12-aadA2-qacEΔ1/sul1 within the class 1 integron is highly conserved. In addition, the class 1 integron and encapsulated sul1 are significantly enriched in Enterobacteriaceae in NCBI and UniProt databases. Conclusion: Our study suggests that the horizontal transfer of TMP/SMX resistance via class 1 integron is most frequently occurred within Enterobacteriaceae and has spread to a wide range of sources including soil, poultry, and marine water.

Treating type 2 diabetes (T2D) patients with sodium–glucose cotransporter 2 (SGLT2) inhibitors may be associated with an increased risk of urinary tract infections (UTIs), such as diabetes-induced asymptomatic bacteriuria. Pyuria—a condition wherein leukocytes are detected in the urine—is a predictor of UTIs. The aim of this study was to examine the urinary microbiome of Taiwanese T2D patients, with or without pyuria, undergoing SGLT2 treatment. We recruited seven T2D patients, recorded their clinical and biochemical characteristics, and collected their urine samples for 16S metagenomic sequencing. The primary outcomes were the diversity of urinary microbiota and the relative abundance of different species. We found that the microbiome of the pyuria group was significantly less diverse than the non-pyuria group (0.24 ± 0.04 vs. 2.21 ± 0.28, p = 0.002), while the number of operational taxonomic units did not differ significantly (763.5 ± 78.67 and 747 ± 141.3, p = 0.92). Escherichia-Shigella spp. dominated the microbiome of the pyuria group (97.4%–99.4%), and these patients tended to have more comorbidities. In conclusion, pyuria is associated with urinary microbiota dysbiosis in T2D patients being treated with SGLT2 inhibitors.

Background/purpose: This study aimed to investigate the in vitro susceptibilities of carbapenem-non-susceptible Pseudomonas aeruginosa (CNSPA) and Acinetobacter baumannii (CNSAB) isolates to cefiderocol, novel β-lactamase inhibitor (BLI) combinations, new tetracycline analogues, and other comparative antibiotics. Methods: In total, 405 non-duplicate bacteremic CNSPA (n = 150) and CNSAB (n = 255) isolates were collected from 16 hospitals in Taiwan between 2018 and 2020. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method, and susceptibilities were interpreted according to the relevant guidelines or in accordance with results of previous studies and non-species-related pharmacokinetic/pharmacodynamic data. Results: Among the isolates tested, cefiderocol demonstrated potent in vitro activity against CNSPA (MIC50/90, 0.25/1 mg/L; 100% of isolates were inhibited at ≤4 mg/L) and CNSAB (MIC50/90, 0.5/2 mg/L; 94.9% of isolates were inhibited at ≤4 mg/L) isolates. More than 80% of CNSPA isolates were susceptible to cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and amikacin, based on breakpoints established by the Clinical and Laboratory Standards Institute. Activities of new BLI combinations varied significantly. Tetracycline analogues, including tigecycline (MIC50/90, 1/2 mg/L; 92.5% of CNSAB isolates were inhibited at ≤2 mg/L) and eravacycline (MIC50/90, 0.5/1 mg/L; 99.6% of CNSAB isolates were inhibited at ≤2 mg/L) exhibited more potent in vitro activity against CNSAB than omadacycline (MIC50/90, 4/8 mg/L). Conclusions: The spread of CNSPA and CNSAB poses a major challenge to global health. Significant resistance be developed even before a novel agent becomes commercially available. The development of on-site antimicrobial susceptibility tests for these novel agents is of great clinical importance.

ABSTRACT Polyp bail-out constitutes both a stress response and an asexual reproductive strategy that potentially facilitates dispersal of some scleractinian corals, including several dominant reef-building taxa in the family Pocilloporidae. Recent studies have proposed that microorganisms may be involved in onset and progression of polyp bail-out. However, changes in the coral microbiome during polyp bail-out have not been investigated. In this study, we induced polyp bail-out in Pocillopora corals using hypersaline and hyperthermal methods. Bacterial community dynamics during bail-out induction were examined using the V5-V6 region of the 16S-rRNA gene. From 70 16S-rRNA gene libraries constructed from coral tissues, 1,980 OTUs were identified. Gammaproteobacteria and Alphaproteobacteria consistently constituted the dominant bacterial taxa in all coral tissue samples. Onset of polyp bail-out was characterized by increased relative abundance of Alphaproteobacteria and decreased abundance of Gammaproteobacteria in both induction experiments, with the shift being more prominent in response to elevated temperature than to elevated salinity. Four OTUs, affiliated with Thalassospira, Marisediminitalea, Rhodobacteraceae, and Myxococcales, showed concurrent abundance increases at the onset of polyp bail-out in both experiments, suggesting potential microbial causes of this coral stress response. IMPORTANCE Polyp bail-out represents both a stress response and an asexual reproductive strategy with significant implications for reshaping tropical coral reefs in response to global climate change. Although earlier studies have suggested that coral-associated microbiomes likely contribute to initiation of polyp bail-out in scleractinian corals, there have been no studies of coral microbiome shifts during polyp bail-out. In this study, we present the first investigation of changes in bacterial symbionts during two experiments in which polyp bail-out was induced by different environmental stressors. These results provide a background of coral microbiome dynamics during polyp bail-out development. Increases in abundance of Thalassospira, Marisediminitalea, Rhodobacteraceae, and Myxococcales that occurred in both experiments suggest that these bacteria are potential microbial causes of polyp bail-out, shedding light on the proximal triggering mechanism of this coral stress response.

Background: Antimicrobial resistance surveillance is essential for empiric antibiotic prescribing, infection prevention and control policies and to drive novel antibiotic discovery. However, most existing surveillance systems are isolate-based without supporting patient-based clinical data, and not widely implemented especially in low- and middle-income countries (LMICs). Methods: A Clinically-Oriented Antimicrobial Resistance Surveillance Network (ACORN) II is a large-scale multicentre protocol which builds on the WHO Global Antimicrobial Resistance and Use Surveillance System to estimate syndromic and pathogen outcomes along with associated health economic costs. ACORN-healthcare associated infection (ACORN-HAI) is an extension study which focuses on healthcare-associated bloodstream infections and ventilator-associated pneumonia. Our main aim is to implement an efficient clinically-oriented antimicrobial resistance surveillance system, which can be incorporated as part of routine workflow in hospitals in LMICs. These surveillance systems include hospitalised patients of any age with clinically compatible acute community-acquired or healthcare-associated bacterial infection syndromes, and who were prescribed parenteral antibiotics. Diagnostic stewardship activities will be implemented to optimise microbiology culture specimen collection practices. Basic patient characteristics, clinician diagnosis, empiric treatment, infection severity and risk factors for HAI are recorded on enrolment and during 28-day follow-up. An R Shiny application can be used offline and online for merging clinical and microbiology data, and generating collated reports to inform local antibiotic stewardship and infection control policies. Discussion: ACORN II is a comprehensive antimicrobial resistance surveillance activity which advocates pragmatic implementation and prioritises improving local diagnostic and antibiotic prescribing practices through patient-centred data collection. These data can be rapidly communicated to local physicians and infection prevention and control teams. Relative ease of data collection promotes sustainability and maximises participation and scalability. With ACORN-HAI as an example, ACORN II has the capacity to accommodate extensions to investigate further specific questions of interest.

Objectives: To explore the in vitro antimicrobial susceptibility among clinically important Gram-negative bacteria (GNB) in Taiwan. Methods: From 2016 through 2018, a total of 5458 GNB isolates, including Escherichia coli (n = 1545), Klebsiella pneumoniae (n = 1255), Enterobacter species (n = 259), Pseudomonas aeruginosa (n = 1127), Acinetobacter baumannii complex (n = 368), and Stenotrophomonas maltophilia (n = 179), were collected. The susceptibility results were summarized by the breakpoints of minimum inhibitory concentration (MIC) of CLSI 2020, EUCAST 2020 (for colistin), or published articles (for ceftolozane/tazobactam). The resistance genes among multidrug-resistant (MDR) or extensively drug-resistant (XDR)-GNB were investigated by multiplex PCR. Results: Significantly higher rates of non-susceptibility (NS) to ertapenem and carbapenemase production, predominantly KPC and OXA-48-like beta-lactamase, were observed in Enterobacterales isolates causing respiratory tract infection than those causing complicated urinary tract or intra-abdominal infection (12.7%/3.44% vs. 5.7%/0.76% or 7.7%/0.97%, respectively). Isolates of Enterobacter species showed higher rates of phenotypic extended-spectrum β-lactamase and NS to ertapenem than E. coli or K. pneumoniae isolates. Although moderate activity (54–83%) was observed against most potential AmpC-producing Enterobacterales isolates, ceftolozane/tazobactam exhibited poor in vitro (44.7–47.4%) activity against phenotypic AmpC Enterobacter cloacae isolates. Additionally, 251 (22.3%) P. aeruginosa isolates exhibited the carbapenem-NS phenotype, and their MDR and XDR rate was 63.3% and 33.5%, respectively. Fifteen (75%) of twenty Burkholderia cenocepacia complex isolates were inhibited by ceftolozane/tazobactam at MICs of ≤4 μg/mL. Conclusions: With the increase in antibiotic resistance in Taiwan, it is imperative to periodically monitor the susceptibility profiles of clinically important GNB.

Abstract Cardiovascular disease (CVD) is strongly associated with the gut microbiota and its metabolites, including trimethylamine-N-oxide (TMAO), formed from metaorganismal metabolism of ʟ-carnitine. Raw garlic juice, with allicin as its primary compound, exhibits considerable effects on the gut microbiota. This study validated the benefits of raw garlic juice against CVD risk via modulation of the gut microbiota and its metabolites. Allicin supplementation significantly decreased serum TMAO in ʟ-carnitine-fed C57BL/6 J mice, reduced aortic lesions, and altered the fecal microbiota in carnitine-induced, atherosclerosis-prone, apolipoprotein E-deficient (ApoE−/−) mice. In human subjects exhibiting high-TMAO production, raw garlic juice intake for a week reduced TMAO formation, improved gut microbial diversity, and increased the relative abundances of beneficial bacteria. In in vitro and ex vivo studies, raw garlic juice and allicin inhibited γ-butyrobetaine (γBB) and trimethylamine production by the gut microbiota. Thus, raw garlic juice and allicin can potentially prevent cardiovascular disease by decreasing TMAO production via gut microbiota modulation.

The coronavirus disease (COVID-19) outbreak has turned the world upside down bringing about a massive impact on society due to enforced measures such as the curtailment of personal travel and limitations on economic activities. The global pandemic resulted in numerous people spending their time at home, working, and learning from home hence exposing them to air contaminants of outdoor and indoor origins. COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which spreads by airborne transmission. The viruses found indoors are linked to the building's ventilation system quality. The ventilation flow in an indoor environment controls the movement and advection of any aerosols, pollutants, and Carbon Dioxide (CO2) created by indoor sources/occupants; the quantity of CO2 can be measured by sensors. Indoor CO2 monitoring is a technique used to track a person's COVID-19 risk, but high or low CO2 levels do not necessarily mean that the COVID-19 virus is present in the air. CO2 monitors, in short, can help inform an individual whether they are breathing in clean air. In terms of COVID-19 risk mitigation strategies, intelligent indoor monitoring systems use various sensors that are available in the marketplace. This work presents a review of scientific articles that influence intelligent monitoring development and indoor environmental quality management system. The paper underlines that the non-dispersive infrared (NDIR) sensor and ESP8266 microcontroller support the development of low-cost indoor air monitoring at learning facilities.

Background: Coronavirus Disease 2019 (COVID-19) is rapidly transmitted from person to person, causing global pandemic since December 2019. Instantly detecting COVID-19 is crucial for epidemic prevention. In this study, olfactory dysfunction is a significant symptom in mild to moderate COVID-19 patients but relatively rare in other respiratory viral infections. The Taiwan smell identification test (TWSIT) is a speedy and inexpensive option for accurately distinguishing anosmia that also quantifies the degree of anosmia. Using TWSIT in the outpatient clinic for early identifying the patients with mild to moderate COVID-19 can be promising. Methods: Nineteen patients confirmed COVID-19 in central Taiwan were collected and divided into two groups: olfactory dysfunction and non-olfactory dysfunction. Demographic characteristics, laboratory findings, and the results of the olfactory test were compared between these two groups. Findings: Thirteen (68.4%) of the 19 patients had olfactory dysfunction. The patients with olfactory dysfunction were younger than those without this symptom. The statistical difference in age distribution was significant between these two groups (IQR: 25.5–35.5 vs. IQR: 32.5–60.3; p-value: 0.012). There was no significant difference in gender, smoking history, comorbidities, travel history, respiratory tract infection symptoms, and laboratory findings between these two groups. Conclusion: This study demonstrated that young adults were prone to develop olfactory dysfunctions. In the flu season, olfactory dysfunction is considered a specific screening criterion for early detecting COVID-19 in the community. TWSIT can serve as a decent test for quantifying and qualifying olfactory dysfunction.

ABSTRACT Autophagy is a natural defense mechanism that protects the host against pathogens. We previously demonstrated that mycobacterial infection upregulated tumor necrosis factor-like weak inducer of apoptosis (TWEAK) to promote autophagy and mycobacterial autophagosome maturation through activation of AMP-activated protein kinase (AMPK). Fibroblast growth factor-inducible 14 (Fn14) is the receptor of TWEAK. But the role of Fn14 in mycobacterial infection remains elusive. Herein, we observed increased expression of Fn14 in peripheral blood mononuclear cells of active tuberculosis (TB) patients. Downregulation of cellular Fn14 enhanced mycobacterial survival in macrophages. Conversely, Fn14 overexpression inhibited mycobacterial growth, suggesting that Fn14 can inhibit mycobacterial infection. The in vitro results revealed that TWEAK-promoted mycobacterial phagosome maturation is Fn14-dependent. We demonstrated that TWEAK-Fn14 signaling promotes oxidative stress to enhance the expression of stromal interaction molecule 1 (STIM1) and its activation of the Ca2+ channel ORAI1. Elevated calcium influx stimulated the activation of CaMCCK2 (calcium/calmodulin-dependent protein kinase kinase 2) and its downstream effector AMPK, thus inducing autophagy in early infection. Persistently TWEAK-Fn14 signaling caused cell death in late infection by reducing mitochondrial membrane potential, leading to mitochondrial ROS accumulation, and activating cell death-associated proteins. Genetic Fn14 deficiency or TWEAK blockers decreased oxidative stress-induced calcium influx, thus suppressing autophagy and cell death in mycobacteria-infected macrophages, and resulting in elevated mycobacterial survival. We propose that the TWEAK-Fn14 axis and calcium influx could be manipulated for anti-TB therapeutic purposes. Our results offer a new molecular machinery to understand the association between the TWEAK-Fn14 axis, calcium influx, and mycobacterial infection. IMPORTANCE Tuberculosis remains a major cause of morbidity and mortality worldwide. We previously demonstrated a relationship between TWEAK and activation of the autophagic machinery, which promotes anti-mycobacterial immunity. The TWEAK-Fn14 axis is multi-functional and involved in the pathogenesis of many diseases, thus blockade of TWEAK-Fn14 axis has been considered as a potential therapeutic target. Here, we demonstrated that the TWEAK-Fn14 axis plays a novel role in anti-mycobacterial infection by regulating calcium-associated autophagy. Persistently, TWEAK-Fn14 signaling caused cell death in late infection by reducing mitochondrial membrane potential, leading to mitochondrial ROS accumulation, and activating cell death-associated proteins. TWEAK blocker or Fn14 deficiency could suppress oxidative stress and calcium-associated autophagy, resulting in elevated mycobacterial survival. We propose that the TWEAK-Fn14 axis and calcium influx could be manipulated for anti-TB therapeutic purposes. This study offers a new molecular machinery to understand the association between the TWEAK-Fn14 axis, calcium influx, and mycobacterial infection.

ABSTRACT Accurate identification of Elizabethkingia species mostly requires the use of molecular techniques, and 16S rRNA gene sequencing is generally considered the method of choice. In this study, we evaluated the effect of intraspecific diversity among the multiple copies of the 16S rRNA gene on the accuracy of species identification in the genus Elizabethkingia. Sequences of 16S rRNA genes obtained from the 32 complete whole-genome sequences of Elizabethkingia deposited in GenBank and from 218 clinical isolates collected from 5 hospitals in Taiwan were analyzed. Four or five copies of 16S rRNA were identified in the Elizabethkingia species with complete genome sequences. The dissimilarity among the copies of the16S rRNA gene was

ABSTRACT: Objectives: The aim of this study was to investigate the trends in serotypes and in vitro antimicrobial susceptibility of Streptococcus pneumoniae causing adult invasive pneumococcal disease (IPD) to dalbavancin, telavancin, tedizolid, eravacycline, omadacycline and other comparator antibiotics from 2017–2020 following implementation of the 13-valent pneumococcal conjugate vaccine (PCV-13) and during the COVID-19 (coronavirus disease 2019) pandemic. Methods: During the study period, 237 S. pneumoniae isolates were collected from non-duplicate patients, covering 15.0% of IPD cases in Taiwan. Antimicrobial susceptibility testing was performed using a Sensititre® system. A latex agglutination method (ImmuLex™ Pneumotest Kit) was used to determine serotypes. Results: Susceptibility rates were high for vancomycin (100%), teicoplanin (100%) and linezolid (100%), followed by ceftaroline (non-meningitis) (98.3%), moxifloxacin (94.9%) and quinupristin/dalfopristin (89.9%). MIC50 and MIC90 values of dalbavancin, telavancin, tedizolid, eravacycline and omadacycline were generally low. Non-vaccine serotype 23A was the leading cause of IPD across the adult age range. Isolates of serotype 15B were slightly fewer than those of PCV-13 serotypes in patients aged ≥65 years. The overall case fatality rate was 15.2% (36/237) but was especially high for non-PCV-13 serotype 15B (21.4%; 3/14). Vaccine coverage was 44.7% for PCV-13 and 49.4% for the 23-valent pneumococcal polysaccharide vaccine (PPSV-23), but was 57% for both PCV-13 and PPSV-23. Conclusion: The incidence of IPD was stationary after PCV-13 introduction and only dramatically decreased in the COVID-19 pandemic in 2020. The MIC50 and MIC90 values of dalbavancin, telavancin, tedizolid, eravacycline, omadacycline were generally low for S. pneumoniae causing adult IPD.

The first imported case of XDR typhoid fever in Taiwan contracted with a bacterial strain, which was most closely related to the blaCTX-M-15-carrying strains linked to Pakistan. Meropenem, in combination with an antimicrobial with intracellular activity against Salmonella, should be used for the treatment of XDR typhoid fever.

Background: Shewanella algae is a zoonotic pathogen that poses a serious health threat to immunocompromised hosts. Treatment of S. algae infections is challenging due to the pathogen's intrinsic resistance to a variety of β-lactam antibiotics. Therapeutic options have become further limited by the emergence of quinolone-resistant strains. Currently, there are few studies concerning the genetic and molecular mechanisms underlying acquired quinolones resistance in S. algae. qnrA was once proposed as the candidate gene related to quinolones resistance in S. algae. However, recent studies demonstrated qnrA are highly conservative and does not confer resistance to quinolones in S. algae. Methods: A total of 27 non-duplicated isolates of S. algae strains were examined. MICs of ciprofloxacin were determined using Vitek 2. Whole genome sequencing was performed using MiSeq platform. Comprehensive Antibiotic Resistance Database and ResFinder were used for annotation of quinolones resistance genes. Multiple sequence alignment by EMBOSS Clustal Omega were used to identified mutation in quinolone resistance-determining regions. To investigation of the alteration of protein structure induced by mutation, in silico molecular docking studies was conducted using Accryl Discovery studio visualizer. Results: All S. algae harbored the quinolone-resistance associated genes (qnrA, gyrA, gyrB, parC, and parE) regardless its resistance to ciprofloxacin. Comparison of these genomes identified a nonsynonymous mutation (S83V) in chromosome-encoded gyrase subunits (GyrA) in quinolone-resistant strain. We found this mutation disrupts the water-metal ion bridge, reduces the affinity of the quinolone-enzyme complex for the metal ions and therefore decrease the capability of quinolones to stabilize cleavage complexes. Conclusions: The study provides insight into the quinolone resistance mechanisms in S. algae, which would be helpful for the evolution of antibiotic resistance in this bacterium.

Concurrent infections caused by multiple fungal pathogens in immunocompromised patients can pose diagnostic and treatment challenges. Here, we presented the first reported case in Taiwan of an AIDS patient who had concurrent infection with Cryptococcus neoformans meningitis and Talaromyces amestolkiae lymphadenopathy. The patient presented with an enlarged inguinal lymph node and was diagnosed with T. amestolkiae lymphadenitis. The species T. amestolkiae was identified using DNA sequencing, which had the capability of differentiating it from other Talaromyces species. The patient was discharged from the hospital following treatment with amphotericin B and subsequent administration of voriconazole. This case highlights the importance of maintaining a suspicion of co-infections and utilizing appropriate diagnostic tools, such as DNA sequencing, to identify possible pathogens. Further studies are needed to determine the optimal treatment for T. amestolkiae and other co-infecting fungal pathogens.

Accurate diagnosis of chronic, non-healing wounds is challenging and time-consuming because it can be caused by a variety of etiologies. This brief report presents an unusual case of a chronic wound lasting for 10 months investigated by deep metagenomic sequencing. Epstein-Barr virus (EBV) was identified in the wound and subsequently validated by in situ hybridization. Histopathologic examination eventually revealed that the non-healing wound was due to an EBV-associated NK/T cell lymphoma. By identifying mutations across the viral genome, the virus was classified as Type I EBV and clustered with others of geographic proximity. Our results suggest that metagenomic shotgun sequencing can not only rapidly and accurately identify the presence of underlying pathogens but also provide strain-level resolution for the surveillance of viral epidemiology.

Abstract Nanopore sequencing has been widely used for the reconstruction of microbial genomes. Owing to higher error rates, errors on the genome are corrected via neural networks trained by Nanopore reads. However, the systematic errors usually remain uncorrected. This paper designs a model that is trained by homologous sequences for the correction of Nanopore systematic errors. The developed program, Homopolish, outperforms Medaka and HELEN in bacteria, viruses, fungi, and metagenomic datasets. When combined with Medaka/HELEN, the genome quality can exceed Q50 on R9.4 flow cells. We show that Nanopore-only sequencing can produce high-quality microbial genomes sufficient for downstream analysis.

Abstract Although most COVID‐19 patients feel their olfactory function returns to normal, the smell test demonstrates that a mild impairment of the olfactory function may have remained. Therefore, their olfactory function should be evaluated by a smell test.

Abstract The capability of gut microbiota in degrading foods and drugs administered orally can result in diversified efficacies and toxicity interpersonally and cause significant impact on human health. Production of atherogenic trimethylamine N-oxide (TMAO) from carnitine is a gut microbiota-directed pathway and varies widely among individuals. Here, we demonstrated a personalized TMAO formation and carnitine bioavailability from carnitine supplements by differentiating individual TMAO productivities with a recently developed oral carnitine challenge test (OCCT). By exploring gut microbiome in subjects characterized by TMAO producer phenotypes, we identified 39 operational taxonomy units that were highly correlated to TMAO productivity, including Emergencia timonensis, which has been recently discovered to convert γ-butyrobetaine to TMA in vitro. A microbiome-based random forest classifier was therefore constructed to predict the TMAO producer phenotype (AUROC = 0.81) which was then validated with an external cohort (AUROC = 0.80). A novel bacterium called Ihubacter massiliensis was also discovered to be a key microbe for TMA/TMAO production by using an OCCT-based humanized gnotobiotic mice model. Simply combining the presence of E. timonensis and I. massiliensis could account for 43% of high TMAO producers with 97% specificity. Collectively, this human gut microbiota phenotype-directed approach offers potential for developing precision medicine and provides insights into translational research. Video Abstract

By the request of the Minister of Health and Welfare, NHRI Biobank was assigned to establish a COVID-19 biobank in early Feb, 2020 to collect COVID-19 patients’ blood samples for Taiwan researchers and industries in an emergent way. It was set up in less than 3 weeks and quickly opened for application. By August 5, 2020, this COVID-19 biobank has collected 165 blood samples of 110 patients from more than 10 hospitals across north, middle and south part of Taiwan, including both COVID-19 (+) and (-) pneumonia patients. This biobank can provide applicants with biosamples, such as serum, DNA and RNA, and also the clinical and genomic data, so as to accelerate the COVID-19 treatment and prevention research in Taiwan. This COID-19 biobank already received 15 applications. It has become the most important research resource for the COVID-19 pandemic in Taiwan, including new screening reagents, disease mechanism, the variable human responses and epidemic preventions. Since it is publicly available for both academic and industrial applicants.

We reported two cases with community-acquired pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who returned from Wuhan, China in January, 2020. The reported cases highlight non-specific clinical presentations of 2019 novel coronavirus disease (COVID-19) as well as the importance of rapid laboratory-based diagnosis.

Abstract. Rationale:. Coronavirus disease 2019 (COVID-19) is a systemic disease with major clinical manifestations in the respiratory system. However, thyroid involvement has also been reported. We present a case of hypothyroidism with ventricular tachycardia following diagnosis with COVID-19. Patient concerns:. A 77-year-old man was admitted to the isolation ward due to COVID-19. After respiratory support and medical treatment, the patient was successfully weaned off the ventilator. However, an episode of short-run ventricular tachycardia was detected, and primary hypothyroidism was also diagnosed. Diagnosis:. Ventricular tachycardia was detected by electrocardiography. Interventions:. Intravenous amiodarone administration and oral levothyroxine replacement. Outcomes:. No arrhythmia detected following treatment. Lessons:. Awareness of the association between hypothyroidism and COVID-19 is important in preventing possible complications.

ABSTRACT Antibiotics used as growth promoters in livestock and animal husbandry can be detected in animal-derived food. Epidemiological studies have indicated that exposure to these antibiotic residues in food may be associated with childhood obesity. Herein, the effect of exposure to a residual dose of tylosin—an antibiotic growth promoter—on host metabolism and gut microbiota was explored in vivo. Theoretical maximal daily intake (TMDI) doses of tylosin were found to facilitate high-fat-diet-induced obesity, induce insulin resistance, and perturb gut microbiota composition in mice. The obesity-related phenotypes were transferrable to germfree recipient mice, indicating that the effects of a TMDI dose of tylosin on obesity and insulin resistance occurred mainly via alteration of the gut microbiota. Tylosin TMDI exposure restricted to early life, the critical period of gut microbiota development, altered the abundance of specific bacteria related to host metabolic homeostasis later in life. Moreover, early-life exposure to tylosin TMDI doses was sufficient to modify the ratio of primary to secondary bile acids, thereby inducing lasting metabolic consequences via the downstream FGF15 signaling pathway. Altogether, these findings demonstrate that exposure to very low doses of antibiotic residues, whether continuously or in early life, could exert long-lasting effects on host metabolism by altering the gut microbiota and its metabolites. IMPORTANCE This study demonstrates that even with limited exposure in early life, a residual dose of tylosin might cause long-lasting metabolic disturbances by altering the gut microbiota and its metabolites. Our findings reveal that the gut microbiota is susceptible to previously ignored environmental factors.

Coral endolithic microbes can be an important nutrients support for hosts while under stresses. Previous studies have found that the endolithic microbial composition of a single coral species can be biogeographical diverse. However, the potential environmental factors, such as salinity, temperature, pH, and nutrient, that might influence the composition of the endolithic microbes remain unclear. In this study, we used both amplicon sequence variants (ASV) and a kmer-based taxonomic unit (KTU) to characterize the endolithic bacterial constitution of Isopora spp. located in the western Pacific Ocean—where it is subjected to the Kuroshio Current (in Okinawa, Japan and Green Island, Taiwan)—and the South China Sea (Dongsha Atoll). The endolithic bacterial community compositions showed a significant geographical difference, and we suggest that the ocean current and primary productivity are the most essential environmental factors influencing the bacterial communities in the skeleton of Isopora spp. In addition, our results showed that, technically, compared to ASV, bacterial composition based on KTU avoids extreme data, making it a suitable tool for explaining the associations between microbes and environmental factors.